NZ525225A - Pyridinone derivatives that inhibit the enzyme lipoprotein associated phospholipase A2 (Lp-PLA2) for the treatment of atherosclerosis - Google Patents
Pyridinone derivatives that inhibit the enzyme lipoprotein associated phospholipase A2 (Lp-PLA2) for the treatment of atherosclerosisInfo
- Publication number
- NZ525225A NZ525225A NZ525225A NZ52522501A NZ525225A NZ 525225 A NZ525225 A NZ 525225A NZ 525225 A NZ525225 A NZ 525225A NZ 52522501 A NZ52522501 A NZ 52522501A NZ 525225 A NZ525225 A NZ 525225A
- Authority
- NZ
- New Zealand
- Prior art keywords
- int
- ethyl
- alkyl
- oxo
- compound
- Prior art date
Links
- 102000016752 1-Alkyl-2-acetylglycerophosphocholine Esterase Human genes 0.000 title claims abstract description 18
- 108010024976 Asparaginase Proteins 0.000 title claims abstract description 18
- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 13
- 150000005299 pyridinones Chemical class 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 130
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 claims description 109
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 68
- -1 4-(phenyl)phenyl Chemical group 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 102000004190 Enzymes Human genes 0.000 claims description 14
- 108090000790 Enzymes Proteins 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000005605 benzo group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 7
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000005864 Sulphur Chemical group 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical class CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 3
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 2
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 5
- 239000000758 substrate Substances 0.000 claims 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 238000003556 assay Methods 0.000 claims 2
- 239000000872 buffer Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims 1
- 239000007995 HEPES buffer Substances 0.000 claims 1
- 229920002684 Sepharose Polymers 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 238000002835 absorbance Methods 0.000 claims 1
- 238000001042 affinity chromatography Methods 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 238000005349 anion exchange Methods 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
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- 238000000108 ultra-filtration Methods 0.000 claims 1
- 241000701447 unidentified baculovirus Species 0.000 claims 1
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- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 124
- 239000003112 inhibitor Substances 0.000 abstract description 12
- 238000002360 preparation method Methods 0.000 abstract description 7
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 abstract description 3
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- 239000000203 mixture Substances 0.000 description 75
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 238000005160 1H NMR spectroscopy Methods 0.000 description 56
- 239000007787 solid Substances 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
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- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- BRKRUKCBFPJFBN-UHFFFAOYSA-N tert-butyl 2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxoquinolin-1-yl]acetate Chemical compound C=1C(=O)C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C=1SCC1=CC=C(F)C=C1 BRKRUKCBFPJFBN-UHFFFAOYSA-N 0.000 description 1
- UZYMYLUCRNBLSQ-UHFFFAOYSA-N tert-butyl 2-[2-[2-(2,3-difluorophenyl)ethyl]-4-oxoquinolin-1-yl]acetate Chemical compound C=1C(=O)C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C=1CCC1=CC=CC(F)=C1F UZYMYLUCRNBLSQ-UHFFFAOYSA-N 0.000 description 1
- GBZQXKJYYKKHEN-UHFFFAOYSA-N tert-butyl 2-[2-[2-(3-chlorophenyl)ethyl]-4-oxoquinolin-1-yl]acetate Chemical compound C=1C(=O)C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C=1CCC1=CC=CC(Cl)=C1 GBZQXKJYYKKHEN-UHFFFAOYSA-N 0.000 description 1
- CRULPQFRIIODJP-UHFFFAOYSA-N tert-butyl 2-[2-[2-(3-fluorophenyl)ethyl]-4-oxoquinolin-1-yl]acetate Chemical compound C=1C(=O)C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C=1CCC1=CC=CC(F)=C1 CRULPQFRIIODJP-UHFFFAOYSA-N 0.000 description 1
- TWMKBLRJGYRKBV-UHFFFAOYSA-N tert-butyl 2-[2-[2-(4-fluorophenyl)ethyl]-4-oxoquinolin-1-yl]acetate Chemical compound C=1C(=O)C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C=1CCC1=CC=C(F)C=C1 TWMKBLRJGYRKBV-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- QYPDJIDQEZDFLS-UHFFFAOYSA-N tert-butyl 2-iodoacetate Chemical compound CC(C)(C)OC(=O)CI QYPDJIDQEZDFLS-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Structural Engineering (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0024808.8A GB0024808D0 (en) | 2000-10-10 | 2000-10-10 | Novel compounds |
| PCT/EP2001/011610 WO2002030904A1 (en) | 2000-10-10 | 2001-10-05 | Pyridinone derivatives for treatment of atherosclerosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ525225A true NZ525225A (en) | 2004-10-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ525225A NZ525225A (en) | 2000-10-10 | 2001-10-05 | Pyridinone derivatives that inhibit the enzyme lipoprotein associated phospholipase A2 (Lp-PLA2) for the treatment of atherosclerosis |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US20040063753A1 (da) |
| EP (2) | EP2258688B1 (da) |
| JP (1) | JP4212354B2 (da) |
| KR (1) | KR100824134B1 (da) |
| CN (2) | CN1280275C (da) |
| AR (1) | AR035349A1 (da) |
| AT (1) | ATE538096T1 (da) |
| AU (2) | AU2002210524B2 (da) |
| BR (1) | BRPI0114576B1 (da) |
| CA (1) | CA2425268C (da) |
| CY (2) | CY1112442T1 (da) |
| CZ (1) | CZ304558B6 (da) |
| DK (2) | DK2258688T3 (da) |
| ES (2) | ES2399325T3 (da) |
| GB (1) | GB0024808D0 (da) |
| GC (1) | GC0000307A (da) |
| HK (2) | HK1144941A1 (da) |
| HU (1) | HU230767B1 (da) |
| IL (2) | IL155278A0 (da) |
| MX (1) | MXPA03003176A (da) |
| MY (1) | MY135766A (da) |
| NO (1) | NO325107B1 (da) |
| NZ (1) | NZ525225A (da) |
| PL (1) | PL207560B1 (da) |
| PT (2) | PT2258688E (da) |
| SI (2) | SI1326841T1 (da) |
| TW (1) | TWI293293B (da) |
| WO (1) | WO2002030904A1 (da) |
| ZA (1) | ZA200302785B (da) |
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| AU2001235466B2 (en) * | 2000-02-16 | 2004-04-22 | Glaxo Group Limited | Pyrimidine-4-one derivatives as LDL-PLA2 inhibitors |
| GB0119793D0 (en) * | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel compounds |
| GB0127139D0 (en) * | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| GB0127140D0 (en) * | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| GB0208279D0 (en) * | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| GB0208280D0 (en) * | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| US20150017671A1 (en) | 2004-04-16 | 2015-01-15 | Yaping Shou | Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity |
| EP1735457A4 (en) | 2004-04-16 | 2007-08-29 | Glaxo Group Ltd | METHODS FOR DETECTING Lp-PLA2 ACTIVITY AND INHIBITION OF Lp-PLA2 ACTIVITY |
| US20080090851A1 (en) * | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US20080090852A1 (en) * | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US7705005B2 (en) * | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
| KR101730290B1 (ko) * | 2007-05-11 | 2017-04-25 | 토마스 제퍼슨 유니버시티 | 신경변성 질환 및 장애의 치료 및 예방 방법 |
| CA2687079A1 (en) * | 2007-05-11 | 2008-11-20 | The Trustees Of The University Of Pennsylvania | Methods of treatment of skin ulcers |
| US9512104B2 (en) * | 2009-07-28 | 2016-12-06 | Auspex Pharmaceuticals, Inc. | Quinolone inhibitors of lipoprotein-associated phospholipase A2 |
| US8575348B2 (en) | 2009-07-28 | 2013-11-05 | Auspex Pharmaceuticals, Inc | Quinolone inhibitors of lipoprotein-associated phospholipase A2 |
| US20120220624A1 (en) * | 2009-10-19 | 2012-08-30 | Tony Siu | Pyrazolo [3,4-b] pyridin-4-one kinase inhibitors |
| US9011821B2 (en) | 2010-06-18 | 2015-04-21 | Whitehead Institute For Biomedical Research | PLA2G16 as a target for antiviral compounds |
| EP2649053B1 (en) | 2010-12-06 | 2015-11-04 | Glaxo Group Limited | Pyrimidinone compounds for use in the treatment of diseases or conditions mediated by lp-pla2 |
| US8859573B2 (en) * | 2010-12-06 | 2014-10-14 | Glaxo Group Limited | Pyrimidinone and pyridinone compounds for use in the treatment of diseases or conditions mediated by Lp-PLA2 |
| US20130267544A1 (en) | 2010-12-17 | 2013-10-10 | Peter Adamson | Use of LP-PLA2 Inhibitors in the Treatment and Prevention of Eye Diseases |
| WO2013000108A1 (zh) * | 2011-06-27 | 2013-01-03 | 中国科学院上海药物研究所 | 唑类杂环化合物、其制备方法、药物组合物和用途 |
| US9273054B2 (en) | 2011-07-27 | 2016-03-01 | Glaxo Group Limited | Substituted pyrimido[1,6-a]pyrimidines as Lp-PLA2 inhibitors |
| EP2739627A4 (en) | 2011-07-27 | 2015-01-21 | Glaxo Group Ltd | 2,3-DIHYDROIMIDAZO [1,2-C] PYRIMIDIN-5 (1H) -ONE COMPOUNDS AND USE AS INHIBITORS OF LP-PLA2 |
| MY172885A (en) | 2011-09-01 | 2019-12-13 | Glaxo Group Ltd | Novel crystal form |
| RU2015135806A (ru) | 2013-01-25 | 2017-03-03 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Соединения |
| UY35276A (es) | 2013-01-25 | 2014-08-29 | Glaxosmithkline Ip Dev Ltd | Nuevos compuestos que inhiben la actividad de Lp-PLA2 |
| KR20150108896A (ko) | 2013-01-25 | 2015-09-30 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Lp-pla2의 억제제로서의 비시클릭 피리미돈 화합물 |
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